DESCRIBE <http://purl.uniprot.org/citations/18303947>

Subject	Predicate	Object
http://purl.uniprot.org/citations/18303947	http://www.w3.org/1999/02/22-rdf-syntax-ns#type	http://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18303947	http://www.w3.org/1999/02/22-rdf-syntax-ns#type	http://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18303947	http://www.w3.org/2000/01/rdf-schema#comment	"NMDA (N-methyl-D-aspartate) receptors and calcium can exert multiple and very divergent effects within neuronal cells, thereby impacting opposing occurrences such as synaptic plasticity and neuronal degeneration. The neuronal Ca2+ sensor Caldendrin is a postsynaptic density component with high similarity to calmodulin. Jacob, a recently identified Caldendrin binding partner, is a novel protein abundantly expressed in limbic brain and cerebral cortex. Strictly depending upon activation of NMDA-type glutamate receptors, Jacob is recruited to neuronal nuclei, resulting in a rapid stripping of synaptic contacts and in a drastically altered morphology of the dendritic tree. Jacob's nuclear trafficking from distal dendrites crucially requires the classical Importin pathway. Caldendrin binds to Jacob's nuclear localization signal in a Ca2+-dependent manner, thereby controlling Jacob's extranuclear localization by competing with the binding of Importin-alpha to Jacob's nuclear localization signal. This competition requires sustained synapto-dendritic Ca2+ levels, which presumably cannot be achieved by activation of extrasynaptic NMDA receptors, but are confined to Ca2+ microdomains such as postsynaptic spines. Extrasynaptic NMDA receptors, as opposed to their synaptic counterparts, trigger the cAMP response element-binding protein (CREB) shut-off pathway, and cell death. We found that nuclear knockdown of Jacob prevents CREB shut-off after extrasynaptic NMDA receptor activation, whereas its nuclear overexpression induces CREB shut-off without NMDA receptor stimulation. Importantly, nuclear knockdown of Jacob attenuates NMDA-induced loss of synaptic contacts, and neuronal degeneration. This defines a novel mechanism of synapse-to-nucleus communication via a synaptic Ca2+-sensor protein, which links the activity of NMDA receptors to nuclear signalling events involved in modelling synapto-dendritic input and NMDA receptor-induced cellular degeneration."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.org/dc/terms/identifier	"doi:10.1371/journal.pbio.0060034"xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.org/dc/terms/identifier	"doi:10.1371/journal.pbio.0060034"xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Richter K."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Richter K."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Landgraf P."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Landgraf P."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Boeckers T.M."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Boeckers T.M."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Gundelfinger E.D."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Gundelfinger E.D."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Kreutz M.R."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Kreutz M.R."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Kreutz M."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Kreutz M."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Garner C.C."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Garner C.C."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Zuschratter W."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Zuschratter W."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Dieterich D.C."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Dieterich D.C."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Landwehr M."xsd:string
http://purl.uniprot.org/citations/18303947	http://purl.uniprot.org/core/author	"Landwehr M."xsd:string